DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• aldehydes to generate acyl radicals. The coupling of this radical to the Ni(0) complex furnishes the acyl−Ni(I) complex, which then proceeds oxidative addition to aryl bromide to generate the pentavalent Ni(III) complex. Lastly, reductive elimination affords the desired ketone and the Ni(I) complex, which

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• through ring-closing reactions that involve the elimination of HBr; notably, ring-closure is successfully promoted in a two-phase system (Scheme 1b). Furthermore, we also report the simple one-pot transformations of lactone derivatives using α-bromolactones as key intermediates. Results and Discussion We

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• oxidative addition, transmetallation, and reductive elimination processes. On the other hand, iron may act as a Lewis acid, activating carbon–carbon multiple bonds via π-binding or heteroatoms via σ-complexes. This can either generate the organoiron complex after nucleophilic attack or produce a carbocation

• is the termination of the reaction through the trapping of the reactive intermediate. Organoiron complexes have been shown to undergo electrophilic trapping with external species or proceed through cross-coupling eventually undergoing reductive elimination. Radical addition will typically conclude

• with the reductive addition or difunctionalization of the π-system; however, it has been demonstrated the radical intermediate can go through a SET oxidation/elimination to recover the initiating π-functionality. In this review, Fe-catalyzed domino coupling reactions involving π-systems will be

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• 16 via β-H elimination using (S)-CPA 4 as a ligand (Scheme 7) [51]. The directing group (NH2) facilitated the C–H activation on the other aromatic ring and ensured its coordination with Pd to form palladacycle I-2 to restrict bond rotations and promote exclusive allylic selectivity via β-H1

• elimination as opposed to styrenyl selectivity. In addition, the methacrylates were used as allyl surrogates to overcome the reactivity problem caused by steric hindrance of 1,1,-disubstituted alkenes, and the electron-withdrawing esters enhance the migratory insertion to form palladacycle I-2. The CPA

• the reaction of 2-substituted indoles with azobenzenes proceeded smoothly in the presence of the chiral phosphoric acid catalyst (R)-CPA 9. At a catalyst loading of 0.2 mol %, the intermediate I-5 was simultaneously cyclized to I-6, followed by β-H elimination and chirality transfer to afford another

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• at reflux temperature in toluene to synthesize the 1,3-oxathiolane lactone 6 via intermediate 5 after elimination of a water molecule. This was further reduced with diisobutylaluminum hydride (DIBAL) in toluene at −78 °C or by lithium tri-tert-butoxyaluminum hydride in THF at 0 °C to obtain lactol 7

• carbon atom while maintaining α-configuration and simultaneous elimination of an acyl group as illustrated in intermediate IV. Further, attack of silylated cytosine on α-chloro-substituted derivative V in an SN2 reaction results in the formation of a glycosidic C–N bond in the β-configured nucleoside

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• first step, vinyl triflate undergoes oxidative addition to give complex 4, which subsequently transmetalates with arylboronic acid to form palladium complex 5. In the case of Pd(PPh3)4, reductive elimination occurs to give enamide 2. However, using catalysts with very bulky ligands, such as Pd(dppf)Cl2

• causes the tautomerization of complex 5 [30] to zwitterionic carbene 6 which can now isomerize through the C–C bond rotation to the thermodynamically more stable palladium complex 7, followed by reductive elimination to enamide 3. A possible isomerization of enamides 2 or 3 in the presence of a catalyst

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• first pathway, the amide product is formed exclusively, while in the second pathway, the elimination of water from the azidohydrine affords a diazoiminium ion, which rearranges to a nitrilium ion by eliminating a nitrogen molecule. The addition of water to this nitrilium ion gives the amide product, but

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• , in path b (a rebound cycle), CuI* is trapped after a SET by the radical intermediate to generate a CuIII species, which undergoes ligand exchange with the nucleophile and reductive elimination to produce the target product and the regenerated CuI catalyst [37][38][40]. 2.2 Visible-light-mediated Cu(I

• to its triplet state CuICN*, in which the fluoroalkyl iodides were reduced to Rf• and I−. Subsequently, the radical Rf• attacks the alkene forming a new alkyl radical species. This radical species is then trapped by CuII(CN)n to generate a CuIII intermediate, which undergoes reductive elimination to

• resulting cyanoalkyl radical then adds to the alkene to form a new alkyl radical. This radical is captured by a high-valent CuIII complex, which undergoes a reductive elimination to give the target product (Scheme 12). In 2018, Reiser and co-worker [63] established a CuII-catalyzed oxo-azidation of vinyl

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• trapped by Cu(II) to deliver the Cu(III) species 12, which undergoes intramolecular annulation and reductive elimination to afford the desired product 8 and regenerate the Cu(I) catalyst. Path b: vinyl radical intermediate 11 is oxidized by Cu(II) to give the cationic vinyl species 14. Finally, the

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• α-lithio ethers, to give convergent access to allylic alcohols and allylic amines, respectively. The process can be considered as proceeding by selective strain-relieving attack (ring-opening) of the lithiated three-membered heterocycle by the lithio ether and then selective β-elimination of lithium

• . This led to the desired allylic alcohol 6 (38%), likely via the selective (ring strain-relieving) 1,2-metalate rearrangement outlined in Scheme 2 (2→3, X = O, LG = OMe), then preferential β-elimination [7][8] of lithium methoxide rather than dilithium oxide. However, also isolated was dodecanal (50

• (Scheme 8). In these cases, the amines are formed by preferential β-elimination [20][21] of lithium methoxide rather than BusNLi2. Synthesis of cyclopropylidene 21 (Scheme 9), suggests a terminal N-Bus-aziridine is capable of being deprotonated by the α-lithio cyclopropane from stannane 11; this contrasts

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• manner as reductive elimination forms during the mercury removal process (Scheme 6). Mercury(II) salts had been effectively used to synthesize five-membered furanose derivatives with high stereoselectivity. Nicotra et al. developed Hg(OAc)2-mediated cyclization of hydroxy-alkene derivative 15 to form α-ᴅ

• derivative 127. The plausible mechanism for the formation of compound 127 proceeded consecutively with π-complex formation, Friedel–Crafts type addition, deprotonation, and finally protonation of alcohol for the elimination of water to get the final product [92]. A Hg(OTf)2-mediated cyclization was utilized

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• with O-phenylhydroxylamine as reagent were not successful and only resulted in the formation of the benzonitriles 16a, 16c and 16e. Presumably, the oximes were formed but were unstable and the facile elimination of phenol took place to liberate the benzonitriles. Finally, the use of this methodology

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• nickel(II) species 2-VI and radical species 2-IV forms a nickel(III) intermediate 2-VII, which undergoes a reductive elimination to afford the desired product 7 and the nickel(I) species 2-VIII. The SET reduction of 2-VIII by the iridium(II) species 2-III regenerates the nickel(0) catalyst 2-V and the

• nickel(III) intermediate 3-VI, which results in the cross-coupled product 7 upon reductive elimination. The SET event between the reduced photocatalyst 3-III and the nickel(0) species 3-IV regenerates both catalysts simultaneously. Further studies by the Doyle group established the α-oxy C(sp3)−H

• (III) species 4-IX, which undergoes reductive elimination to release the desired product 10a. Concurrently, Molander and co-workers also reported a related nickel-catalyzed arylation of α-heteroatom-substituted or benzylic C(sp3)‒H bonds by aryl bromides 3 at room temperature using an iridium

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• KI formed ferrous iodide, which reacts with indole to form the iron bis-indolide 107, followed by reaction with N,N-dimethylmethanethioamide to get the S atom inserted (108). A reductive elimination then generated the bis(indol-3-yl)sulfides 105 along with Fe0, which was re-oxidized by aerial oxygen

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• amounts (< 5% isolated yield, Table 6, entries 7 and 9), due to poor conversion (< 5%, combined N-1 and N-2 (see Supporting Information File 1)). While the latter observation may be due to competing elimination of the alkyl halide under strongly basic conditions [40], the use of a secondary tosylate

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• –H activation involving carbon–metal bond or a mechanism involving the usual metal-mediated coupling pathways comprising oxidative addition, transmetalation and reductive elimination steps, they are beyond the scope of this review and will not be extensively covered herein. Homogeneous and

• /hemiacetal avoiding undesirable elimination to the enamine, or attack at other electrophilic sites in complex substrates. The presence of a fluorine source like diethylaminosulfur trifluoride (DAST) or the Lewis acid boron trifluoride diethyl etherate (BF3·OEt2) result in the formation of reactive iminium or

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• no α-proton to the N-F site proved to be a good choice for fluorinating enolate anions (Scheme 24). The side reaction, involving HF elimination, and which was a problem in reactions with the Barnette’s reagents 4-1 having the α-proton(s) except for 4-1b [26], was avoided here. The HF elimination is a

• β-elimination of HF proved to be an obstacle for the fluorination of strong bases such as phenyllithium. 1-13. N-Fluoro-o-benzenedisulfonimide In 1991, Davis and co-worker reported N-fluoro-o-benzenedisulfonimide (NFOBS, 13-2) as a fluorination reagent. NFOBS was prepared by the direct fluorination

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• elimination to produce 23C, whereby the addition of BPh3 presumably accelerates this process [65]. Subsequently, the manganese species participate in the catalytic cycle by yielding alkynylated product 25. However, the mechanism entailing oxidative addition, followed by reductive elimination could not be

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• key considerations were elimination of electrostatic repulsion (neutral backbone) and synthetic accessibility (simple to make achiral amide linkages) [3]. The design was guided by a simple computer model where the natural sugar-phosphodiester backbone of the Hoogsteen strand of a T•A–T DNA triplex was

• min in mice) through the kidneys after administration to animals by either intravenous or intraperitoneal injection [16]. In another study, PNA elimination half-life in rats was ≈17 minutes and ≈90% of PNA was recovered unchanged in the urine 24 h after administration [17]. To address these problems

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• subsequent elimination of HBr leads to the triazole ring [39]. Another metal-free strategy to 1,4,5-trisubstituted 1,2,3-triazoles 8 was realized by regioselective reaction of aryl azides 7 with enaminones 6 in the presence of triethylamine, water, and ionic liquid (IL). This method exhibits good functional

• investigated by means of DFT calculations using the reaction between enaminone 6a and phenyl azide. TS1 and TS2 have been proposed as two transition states, which then converted to IN1 and IN2 as two possible isomers. The stable final products were achieved via a cascade reaction including the elimination of

• is imine–enamine-tautomerized to afford the intermediate 27. Then, the final triazole compound, as major isomer, is achieved through an intermolecular cyclization process and elimination of one unit of TsNH2 [23]. A general strategy was described for the synthesis of 1,4,5-trisubstituted glycosyl

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• carboxylate-assisted C−H cleavage to deliver copper(II) intermediate A. Next, the copper(III) carboxylate species B is generated. Thereafter, a facile base-assisted ligand exchange is followed by reductive elimination to afford the alkynylated benzamide D. Finally, the desired isoindolone 3 is formed via an

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• than Pd(II)-catalytic types have also been explored. Pd(II)-catalyzed hydroalkylation reactions The σ-alkylpalladium species formed after a carbon nucleophilic attack on an alkene double bond (Scheme 1) have a marked tendency to undergo a hydride β-elimination process that leads to oxidative coupling

• -substituted β-diketones 2a and 2b (61 and 70% yield, respectively). Notably, the unsaturated carbocycles expected from palladium β-hydride elimination were not observed, indicating that an oxidant was not required in the reaction medium to regenerate the Pd(II) species. Later, deuterium-labeling experiments

• counterparts, and so therefore are examples of quaternary centers generated by this means. The tendency of σ-alkylpalladium complexes to undergo a β-hydride elimination process is the major obstacle associated with the development of successful methodologies to promote intermolecular hydroalkylation of

Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• hole-type conductivity with μh = 1.2⋅10−3 cm2⋅V−1⋅s−1. Therein, the thermolysis of a thin film of the device at 220 °C, accompanied by the elimination of Boc groups, led to a significant decrease of the OFET performance. For the example of the polymers 52 series, the importance of the spatial

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• ) [13], from which we recently effected coupling to yield a protected C6 hydroxamate [11]. Accordingly, 1 was stirred with PyBOP and DIPEA in CH2Cl2 for 5 minutes, before 3-aminopropionitrile was added. After stirring for 1.5 hours at room temperature an undesired C4–C5 elimination material 3 was

• isolated as the major product in 35% yield, with only a trace amount of the desired 2 formed (7% yield). The ability of 3-aminopropionitrile to act as a base and trigger this elimination was comparable to results we observed using N,O-dibenzylhydroxylamine as the coupling partner [11]. In the latter

• instance we were able to modify the nucleophile component to O-benzylhydroxylamine and supress unwanted elimination. Unable to do this here, we instead reduced the reaction temperature to 0 °C, maintaining this for 40 minutes. Pleasingly, the yield and product distribution were improved, affording

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• source. Compound 14 could only be purified by recrystallization; all attempts to purify 14 by column chromatography led to complex mixtures of which the only identifiable product was 15. Even recrystallization can be problematic. Heating 14 leads to an elimination reaction that re-forms the initial

• compound 6. It is unclear how the denitration product 15 forms. Elimination of the ether 14 to regenerate the enone 6 is straightforward, but reductive denitration is a taxing reaction that normally requires strongly reducing conditions or a single electron donor. There are examples of milder denitrations

• than three repeats quoted). Possible mechanism for the formation of [2.2]metaparacyclophane 5 and cyclohexadienone cyclophane 6 from [2.2]paracyclophane 1. Conjugate addition of methanol and subsequent elimination. Supporting Information Supporting Information File 208: Metaparacyclophane spectra